7.4 Genetic Screening and Biochemical Pathways

Using many other mutations and the “one gene: one enzyme model”, permitted the genetic dissection of many other biochemical and developmental pathways. The general strategy for a genetic screen for mutations is to expose a population to a mutagen, then look for individuals among the progeny that have defects in the biological process of interest. There are many details that must be considered when designing a genetic screen (e.g. how can recessive alleles be made homozygous). Nevertheless, mutational analysis has been an extremely powerful and efficient tool in identifying and characterizing the genes involved in a wide variety of biological processes, including many genetic diseases in humans.

The video, Genetic Screen, by Animated biology With arpan (2017) on YouTube, discusses the methods used to perform genetic screening.

Forward genetic screening refers to the process of finding the gene or genes responsible for a certain phenotype or biochemical process. One way to identify genes that affect a particular biological process, is to induce random mutations in a large population, and then look for mutants with phenotypes that might be caused by a disruption of a particular biochemical pathway. This is the strategy of mutant screening, and has been used very effectively to identify and understand the molecular components of hundreds of different biological processes. For example, to find the basic biological processes of memory and learning, researchers have screened mutagenized populations of Drosophila to recover flies (or larvae) that lack the normal ability to learn (yes Drosophila can learn). Mutants lack the ability to associate a particular odor with an electric shock. Because of the similarity of biology among all organisms (common descent), some of the genes identified by this mutant screen of a model organism may be relevant to learning and memory in humans, including conditions such as Alzheimer’s disease.

On the other hand, reverse genetic screening refers to the process of creating a mutation in a gene, then identifying the phenotypic consequences of that specific mutant gene on the organism. This method is becoming more useful with the advent of whole genome sequencing. Here, we have identified the gene sequences, but are unsure of what each gene does.

Genetic Screens

In a typical mutant screen, researchers treat a parental population with a mutagen. This may involve soaking seeds in EMS, or mixing a mutagen with the food fed to flies. Usually, no phenotypes are visible among the individuals that are directly exposed to the mutagen because in all the cells every strand of DNA will be affected independently. Thus, the induced mutations will be heterozygous and limited to single cells.

However, what is most important to geneticists are the mutations in the germline of the mutagenized individuals. The germline is defined as the gametes and any of their developmental precursors, and is therefore distinct from the somatic cells (i.e. non-reproductive cells) of the body. Because most induced mutations are recessive, the progeny of mutagenized individuals must be mated in a way that allows the newly induced mutations to become homozygous (or hemizygous).  Strategies for doing this vary between organisms.  In any case, the generation in which induced mutations are expected to show a phenotype can be examined for the presence of novel traits. Once a relevant mutant has been identified, geneticists can begin to make inferences about what the normal function of the mutated gene is, based on its mutant phenotype. This can then be investigated further with molecular genetic techniques to connect the gene function with the external appearance.

The video, Genetic Systems for Detecting Mutation, by Alex Nieves (2020) on YouTube, discusses the Genetic Systems used to detect mutations.


Animated biology With arpan (2017, October 24). Genetic screen (video file). YouTube. https://www.youtube.com/watch?v=q6JrUrrH8e8

Nieves, A. (2020, April 27). Genetic systems for detecting mutation (video file). YouTube. https://www.youtube.com/watch?v=AM60LcYHrcQ


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Open Genetics by Natasha Ramroop Singh, Thompson Rivers University is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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